The objective of the proposed work is the further investigation and characterization of the norepinephrine (NE) receptor coupled adenylate cyclase system in limbic forebrain and in other brain structures with noradrenergic projections. Emphasis will be placed on (a) The elucidation of the molecular mechanisms underlying changed sensitivity of the system including the regulation of the density of NE receptors b) The development of a ligand for the NE receptor moiety that is not beta in nature c) The investigation of the neurobiological consequences of the pharmacologically induced changes in sensitivity of the system and d) An evaluation of the implications of the pharmacological findings for a receptor pathology of affective disorders.